Epigenetic Mediation of Adverse Social Context on Stress Response, Socioemotional Development, and Health in a Population-based Study of Minority and Low SES Children and Adolescents

项目摘要 在一系列健康的儿童和青少年中，存在着明显的种族、民族和社会性别差异 许多成年人的健康差距可以追溯到儿童时期的社会背景不平等。 表观遗传学-对基因组的修饰，而不是核苷酸序列的变化-拥有巨大的希望 作为环境影响和健康状况的潜在指标，可能会长期暴露健康差距 在正常情况下观察到它们之前。在现有的儿童代表性研究的基础上，这项建议将 通过以下方式直接响应PAR-16-355：1)在两个时间点收集2,000名儿童的表观基因组数据 时间，2)描述3个种族/民族和跨SES水平的甲基化模式，以及3)解释 表观遗传学与社会逆境、生物过程和社会情感发展的联系。这个 最重要的假说是DNA甲基化部分地调节了不利的社会环境的影响(即 贫困、严苛的育儿方式、邻里关系混乱、家庭不稳定和父母监禁) 与应激反应相关的生物过程(端粒长度和磨损、皮质醇反应、脱氢表雄酮水平) 以及压力反应行为(行为问题、冒险和弹性)。我们进一步假设 根据种族/民族和SES对逆境的不同暴露和不同反应解释了一些 压力反应和社会情绪发展的差异--因此需要正式比较 同一研究中的种族/民族和社会经济地位。为了进行这项研究，我们使用了脆弱的家庭和儿童 幸福研究(FFCWS)：1998年出生的4898名儿童的全国20个城市和具有代表性的城市样本- 2000年。FFCW提供了独特的非西班牙裔黑人(47%)、西班牙裔(27%)和 因此，这些数据对于研究种族/民族和社会经济地位的差异特别有用。 在出生时、1岁、3岁、5岁、9岁和15岁时对家庭进行了采访--收集了9岁和15岁时的生物数据 15.预期结果将提供以下方面的估计：1)基于群体的表观基因组DNA 3个种族/民族(西班牙裔n=600，非洲裔n=980，欧洲裔)的甲基化措施 N=420)在儿童和青春期，2)社会逆境在整个发展阶段(从宫内到青春期)的关联 15岁)与DNA甲基化有关，3)DNA甲基化与生物应激指标之间的联系 反应(即端粒长度和磨损、皮质醇反应和脱氢表雄酮水平)，4)关联 应激反应行为的发展和甲基化特征之间的关系，以及5)所有这些的比较 3个种族/民族群体和广泛的社会经济共同体之间的关系。

Project Abstract Pronounced disparities exist by race, ethnicity, and SES in children and adolescents across a range of health conditions, and many adult health disparities can be traced to childhood social contextual inequalities. Epigenetics—modifications to the genome that are not changes in nucleotide sequence—holds great promise as potential indicators of contextual effects and health condition, potentially uncovering health disparities long before they are normally observable. Building on an existing representative study of children, this proposal will directly respond to PAR-16-355 by: 1) assembling epigenome-wide data on 2,000 children at two points in time, 2) describing methylation patterns in 3 race/ethnic groups and across SES levels, and 3) explicating epigenetic associations with social adversity, biological processes, and socioemotional development. The overarching hypothesis is that DNA methylation partially mediates the effect of adverse social context (i.e. poverty, harsh parenting, neighborhood disorganization, family instability, and parental incarceration) on biological processes related to stress response (telomere length and attrition, cortisol response, DHEA levels) and stress responsive behaviors (behavioral problems, risk taking, and resilience). We further hypothesize both differential exposure and differential response to adversity by race/ethnicity and SES explains some of the disparity in stress response and socioemotional development—thereby requiring formal comparisons of race/ethnicity and SES in the same study. To conduct this research we utilize the Fragile Families and Child Wellbeing Study (FFCWS): a 20-city nationally and city representative sample of 4898 children born in 1998- 2000. FFCW provides a uniquely high prevalence of non-Hispanic Black (47%), Hispanic (27%), and impoverished families, making the data particularly useful for studying race/ethnic and SES differences. Families were interviewed at birth and at ages 1, 3, 5, 9, and 15—with biological data collected at ages 9 and 15. The expected results will be to provide estimates of: 1) population-based epigenome-wide DNA methylation measures for 3 race/ethnic groups (Hispanic n=600, African ancestry n=980, European ancestry n=420) in childhood and adolescence, 2) associations of social adversity across development (from in utero to age 15) with DNA methylation, 3) associations between DNA methylation and biological measures of stress response (i.e. telomere length and attrition, cortisol response, and DHEA levels), 4) associations between development of stress response behaviors and methylation profiles, and 5) comparisons of all these relationships in 3 race/ethnic groups and across a wide range of SES.